Known in the art are esters of corticoids, intermediate products of their biosynthesis and cytotoxic acids of different structure.
They can be exemplified by esters of pregnenolone and p-di-(2-chloroethyl)aminophenylacetic acid (chlorophenacyl):
3.beta.-hydroxy-5-pregnen-20-one-3.alpha.-p-di(2-chloroethyl)aminophenylace tate ##STR2## and desoxycorticosterone and chlorophenacyl-21-hydroxy-4-pregnen-3,20-dione-21-[p-di(2-chloroethyl)amin ophenylacetate]: ##STR3##
The antitumor properties of these compounds have been studied but insufficiently. There has been established their antitumor activity against Walker carcino-sarcoma W-256, chronic leukemia of rats and certain tumors originating from hormone-depending tissues-cervical carcinoma RShM-5, mammary carcinoma R-13726. However, these compounds have not revealed any activity in respect of lymphoid leukemia L 1210 (cf. Z. P. Sof'ina, N. D. Lagova, I. M. Valueva, Z. V. Kuz'mina, E. N. Shkodinskaya, A. M. Khaletsky. Proceedings of I All-Union Conference on Chemiotherapy of Malignant Tumors, Riga, 1968, p. 441-443; M. Wall, G. Abernethy, F. Carrol, D. Taylor, J. Med. Chem., 1969, 12, No. 5, pp. 810-818; N. D. Lagova. Experimental Oncology 1982, vol. 4, No. 5, p. 38-42).
Known are esters of corticoids, more particularly esters of hydrocortisone and .beta.-chloroethylcarbamic acid; 9.alpha.F,11.beta.,16.alpha., 17.alpha.,26-tetraoxypregna-1,4-diene-3,20-dione-21-[bis-(2-chloroethyl)ca rbamate], 16,17-acetonide ##STR4## and esters of triamcinolone-acetonide and .beta.-chloroethylcarbamic acid: 11.beta.,17.alpha.,21-trihydroxy-pregnene-4-3,20-dione-21-[bis(2-chloroeth yl)carbamate]: ##STR5## The compounds are biologically active. They inhibit growth of cultures of mice fibroblasts L-929 and react with cell receptors. However, these biological effects are reversible (cf. A. Masry, V. Braun, C. Nielsen, W. Pratt, J. Med. Chem., 1977, vol. 20, No. 9, pp. 1134-1139).
Known in the art is an ester of a synthetic corticoid-prednisolone and p-di-(2-chloroethyl)aminophenylbutyric acid (chlorambucyl): pregna-1,4-diene-3,20-dione, 11.beta.17,21-trihydroxy-21-[p-di(2-chloroethyl)aminophenylbutyrate] of the formula: ##STR6## which was give the tradename "Prednimustine" (D. Alftchew, I. Rush. Ann. Chir, Gynaecol. Fenw., 1969, vol. 58, p. 234; J. Kaufmann, G. Hunjura, A. Mittelmann, C. Arengsta, G. Murphy, Cancer. Treat. Rep. 1976, vol. 60, No. 3, pp. 277-279).
The preparation "Prednimustine" is useful in oncological clinic for the treatment of systemic blood diseases and, to a lesser extent--breast cancer. Side effects of "Prednimustine" are associated mainly with hematotoxicity.